This invention relates to a device for the administration of a pharmaceutical composition for treating fungal nail infections. Particularly, the device has an occlusive backing which facilitates the composition""s migration into finger nails, toe nails and the epidermis around the nails.
Conditions such as onychomycosis pose serious problems in dermatology. Onychomycosis is a condition recognized by discoloration beneath toe nails and finger nails along with pain when pressure is placed near or at the site of discoloration. The condition usually affects more than one nail. Various fungi, classified as white superficial fungi, cause the condition. The prevalence of onychomycosis in the general population is in the range of 2-13% and increases to about 15-20% in the 40-60 year old age group.
The current treatment of onychomycosis generally falls into three categories: systemic administration of antifungals; surgical removal of all or part of the nail followed by topical treatment of the exposed tissue; or topical application of conventional creams, lotions, gels or solutions on the infected nail, frequently including the use of bandages to keep these dosage forms in place on the nails. All of these approaches have major drawbacks.
Long term systemic (oral) administration of an antifungal agent for the treatment of onychomycosis has been required to produce a therapeutic effect. For example, oral treatment with the antifungal compound ketoconozole typically requires administration of 200 to 400 mg/day for 6 months before any significant therapeutic benefit is realized. Such long term, high dose systemic therapy can have significant adverse effects. For example, ketoconozole has been reported to have liver toxicity effects and reduces testosterone levels in blood due to adverse effects on the testes. Patient compliance is a problem with such long term therapies especially those which involve serious adverse effects.
Surgical removal of all or part of the nail followed by topical treatment also has severe drawbacks. The pain and discomfort associated with the surgery and the undesirable cosmetic appearance of the nail or nail bed represent significant problems, particularly for female patients or those more sensitive to physical appearance.
Topical therapy has significant problems too. Topical dosage forms such as creams, lotions, gels etc., do not keep the drug in intimate contact with the nail for prolonged periods of time. Bandages have been used to hold drug reservoirs in place in an attempt to enhance absorption of the pharmaceutical agent. However the bandages are thick, awkward, troublesome and generally lead to poor patient compliance.
Hydrophilic and hydrophobic film forming topical antifungal solutions have also been developed. These dosage forms provide improved contact between the drug and the nail, but the films are not occlusive. Moreover, topical formulations for onychomycosis treatment have exclusively tried to deliver the drug to the target site (an infected nail bed) by diffusion across or through the nail.
Human nail is more like hair than stratum corneum with respect to chemical composition and permeability. Nitrogen is the major component of the nail attesting to the nail""s proteinaceous nature. The total lipid content of mature nail is 0.1-1.0%, while the stratum corneum lipid is about 10% w/w. The nail is 100-200 times thicker than the stratum corneum and has a very high affinity and capacity for binding and retaining antifungal drugs. Consequently, little if any drug penetrates through the nail to reach the target site (the nail bed, see FIG. 4, number 16). Because of these reasons, topical therapy for onychomycosis has generally been ineffective.
Onychomycosis is a localized fungal infection of the nail plate and nail bed. The ideal therapy for onychomycosis would maintain very high local tissue concentration of an antifungal agent in the nail and skin, and deliver effective amounts of drug topically to the nail bed, with minimum systemic exposure. Matrix type skin patches are well known in the art, but their advantages for the treatment of onychomycosis have not been recognized. A matrix patch device configured for application over the infected nail and surrounding skin would overcome all the disadvantages of conventional topical therapy for onychomycosis.
It would therefore be desirable to have a matrix patch device which not only enabled the passage of drug compositions into the nail to preclude additional invasive infection but which simultaneously facilitated the transnail and transdermal administration of an antifungal agent to treat the infection directly. The invention herein described accomplishes this and other purposes.
Accordingly, it is a primary objective of the present invention to provide a method for the transdermal/transnail delivery of sufficient amounts of a suitable drug to an affected nail bed and surrounding tissue.
It is an additional object of the present invention to provide a method whereby an occlusive patch is adhered to the treatment site such that the adhesive layer of the patch is maintained in direct diffusional contact with the digit to be treated and where the adhesive layer is adapted to deliver an antifungal agent to the infected site.
These and other objects may be realized by means of an occlusive device suitable for the transdermal and transnail delivery of antifungal pharmaceutically-active agents which are lipophilic or hydrophilic, including salts. The device comprises an occlusive backing layer and a pressure sensitive matrix layer having a first surface adhering to the backing layer and an opposite second surface adapted to be in diffusional contact with the nail and surrounding skin areas.
Matrix type skin patches are known in the art but none have heretofore been developed and configured for application and adhesion to the nail and surrounding skin areas. It has been discovered that such an antifungal pressure sensitive adhesive matrix patch renders it possible to saturate the nail plate with very high concentration of an antifungal agent compared to systemic dosing (with minimal systemic exposure) while administering the antifungal drug to the nail bed, as the target site, via the nail and skin around the nail at much higher rates than would be possible through the nail alone. The invention provides penetrating transdermal/transnail compositions based on the use of a pharmaceutically-active agent dissolved in, or admixed with a biocompatible pressure sensitive adhesive. It may also be advantageous and even preferable to also include an effective amount of one or more penetration enhancing agents as will be more specifically identified below.
The drug enhancer combination is contained in an occlusive device for purposes of holding the composition against the skin or nail surface for administration. Such devices are patches configured for adhesion to the nail surface including a portion of the surrounding tissue in matrix form.
A matrix patch is one where in the drug/enhancer is admixed with a pressure sensitive adhesive to form a matrix. Matrix patches are formed by admixing the drug/adhesive and enhancer if present in a fluid or spreadable form. A uniform depth or thickness of admixture is spread or cast on a protective pealable release liner and a film backing is placed on the opposite side of the admixture to form a film sandwich with the drug/adhesive/enhancer in the center. The film sandwich is then die cut into the appropriate size and pouched in a protective pouch until ready for application. For use, the pealable release liner is removed and the drug/adhesive/enhancer matrix is applied directly to the nail and surrounding skin. The drug and enhancer migrate from within the adhesive matrix to the nail and skin surface. The enhancer, as here presented, functions to increase the flux of drug through the skin and increase the penetration of the drug into and through the nail. Importantly, the occlusive backing of the patch holds the drug against the nail and skin to increase the migration of the drug from the matrix patch into the nail and associated skin.